Numerous preclinical studies have demonstrated multiple health benefits including anti- inflammatory, antioxidant, and chemopreventive effects of dietary polyphenols. These compounds are abundant in plants and have added to the health benefits of many fruits, such as raspberries, pomegranates, and strawberries. As aging population in the U.S. and other developed nations turn their focus from disease treatment to disease prevention, diets high in antioxidants are increasingly sought. Polyphenols, such as ellagic acid which show promise in preventing inflammation and oxidative stress, account for roughly $1.5B of the antioxidant market. While polyphenols demonstrate potent health benefits in in vitro tests, the problems of poor absorption and bioavailability, and high inter-individual efficacy have arisen in in vivo trials. It has become clear that the health benefits of these compounds should be linked to microbial metabolites of polyphenols which have greater tissue availability not to the parent compounds. However, a knowledge gap surrounds the identity of the intestinal microbiota constituents which are capable of metabolizing ellagic acid to urolithins The microbial dependent transformation results in increased absorption of the metabolites and enhanced bioavailability. We will capitalize on our previous experience in isolating specific bacteria from complex microbial ecosystems, to identify and isolate the bacteria responsible for this conversion. Of particular relevance for this application is the role of ellagic acid and the stabile bacterial metabolites, urolithins, in disease prevention. The goal of this Phase I SBIR grant is to identify and isolate the colonic bacteria that metabolize ellagic acid to the bioactive urolithins thereby increasing the absorption and bioavailability of the active compounds. We plan to achieve the above stated goal of this proposal by addressing the following two specific aims:
Aim 1 : Identify the colonic bacterial species that convert ellagitannins to urolithins.
Aim 2 Isolate and propagate bacteria capable of biotransforming ellagic acid to urolithins. The ultimate goal of this project is to identify and commercialize a bacterial product that can be used as a processing aid in the production of plant based dietary products such as juices, jellies, and wines, or as a probiotic, to increase the bioavailable antioxidants and anti-inflammatories and decrease oxidative stress and inflammation in tissue. This contribution is significant because it provides a natural processing scheme to increase the bioavailability of antioxidants across populations and more effectively standardize the dose of the bioactive molecules that can enter the tissues. Furthermore, there is potential for the targeting of tissue specificity and targeted prevention/treatment of inflammatory diseases using a value added dietary approach.

Public Health Relevance

Inflammation and oxidative stress are serious components of multiple diseases including cancer, obesity, atherosclerosis and bowel diseases. While dietary approaches to prevention of these diseases show great promise, there is a significant gap in our knowledge in understanding the interaction of ingested foods and the gut microbiota. The proposed studies will provide invaluable information and develop technology to allow for the targeted delivery of specific, beneficial microbial metabolites to tissues in the body, allowing fo the potential prevention of diseases in a natural manner.

National Institute of Health (NIH)
National Center for Complementary & Alternative Medicine (NCCAM)
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
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Special Emphasis Panel (ZRG1-DKUS-N (10))
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Pontzer, Carol H
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Agro Biosciences, Inc.
United States
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